The purpose of the work described in this proposal is to continue study of the mechanisms of cellular immunity and hypersensitivity. Our aim is to acquire knowledge of basic mechanisms which can be used to rationally manipulate these cellular processes in certain human clinical conditions where enhancement of cellular immunity might lead to prevention or alleviation of disease such as infections or neoplasia, or where suppression might diminish tissue injury caused by cellular hypersensitivity. The proposed investigation is a direct outgrowth of our interests in the interaction of lymphocytes, their mediators and macrophages in cellular immunity. Studies in this project will include further investigations of the mechanism of macrophage activation by lymphocyte mediators, further characterization of the macrophage glycolipid which appears to act as a receptor for MIF, and use of this material to develop affinity chromatographic methods to isolate MIF, analysis of the glycolipid and glycoprotein content of purified macrophage membrane preparations obtained from activated and control macrophages, further purification of migration inhibitory factor, studies on the relationship of mouse MIF and SIRS, a mediator which inhibits antibody formation in vitro and also acts via macrophages, and determining of subtypes of T lymphocytes which produce these mediators. BIBLIOGRAPHIC REFERENCES: Kuhner, A.L., and David, J.R.: Partial characterization of murine migration inhibitory factor (MIF). J. Immunol. 116:140, 1976. David, J.R., and Remold, H.G.: Macrophage activation by lymphocyte mediators and studies on the interaction of macrophage inhibitory factor (MIF) with its target cells. In: IMMUNOBIOLOGY OF THE MACROPHAGE, D.S. Nelson, ed., Academic Press, NY, 1976, p. 401.